ArticleLeukemia2024
Chronic lymphocytic leukemia patient-derived xenografts recapitulate clonal evolution to Richter transformation.
Article in Leukemia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 17 citations in OpenAlex.
- Scaffold-free three-dimensional culture of chronic lymphocytic leukaemia preserves B-T-cell cross-talk and enables drug response profiling.British journal of haematology · 2026Article
- Harnessing PDX and PDX 2.0: the next-generation paradigm for precision oncology and translational breakthroughs.Molecular cancer · 2026Review
- Darunavir analog precursors target mitochondrial metabolism in multiple myeloma and CLL.Cancer cell international · 2025Article
- Unveiling the role of microRNAs, the PI3K/AKT pathway, and their associations in various types of leukemia: a comprehensive review.Blood research · 2025Review
- CLL to Richter syndrome: Integrating network strategies with experiments elucidating disease drivers and personalized therapies.Science advances · 2025Article
- [Establishment of a chronic lymphocytic leukemia mouse model via adoptive transfer of Eμ-TCL1 transgenic splenocytes].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025Article
- A question of TiME: how microenvironmental interactions shape response to immunotherapy in CLL and Richter Transformation.Frontiers in immunology · 2025Review
- CanPharmaceuticals (Basel, Switzerland) · 2024Review
- Mouse models of chronic lymphocytic leukemia and Richter transformation: what we have learnt and what we are missing.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm with a heterogeneous clinical behavior. In 5-10% of patients the disease transforms into a diffuse large-B cell lymphoma known as Richter transformation (RT), which is associated with dismal prognosis. Here, we aimed to establish patient-derived xenograft (PDX) models to study the molecular features and evolution of CLL and RT. We generated two PDXs by injecting CLL (PDX12) and RT (PDX19) cells into immunocompromised NSG mice. Both PDXs were morphologically and phenotypically similar to RT. Whole-genome sequencing analysis at different time points of the PDX evolution revealed a genomic landscape similar to RT tumors from both patients and uncovered an unprecedented RT subclonal heterogeneity and clonal evolution during PDX generation. In PDX12, the transformed cells expanded from a very small subclone already present at the CLL stage. Transcriptomic analysis of PDXs showed a high oxidative phosphorylation (OXPHOS) and low B-cell receptor (BCR) signaling similar to the RT in the patients. IACS-010759, an OXPHOS inhibitor, reduced proliferation, and circumvented resistance to venetoclax. In summary, we have generated new RT-PDX models, one of them from CLL cells that mimicked the evolution of CLL to RT uncovering intrinsic features of RT cells of therapeutical value.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.